Scientists in Manchester, who have developed a stem cell gene therapy to reverse a fatal childhood illness, have agreed to work with a new therapeutics company to test it in a human trial.
University of Manchester and Central Manchester University Hospital NHS Foundation Trust (CMFT) researchers have developed the pioneering approach for Sanfilippo disease (also known as mucopolysaccharidosis type III or MPS III) – a genetic condition for which there is currently no effective treatment.
The most common of the four types of Sanfilippo (type A) affects around 100 children in the UK, or one in 89,000 births, and it is this type that is targeted by the new treatment.
Sanfilippo is caused by a lack of the SGSH enzyme, which helps to break down and recycle long chain sugars. This results in a build-up of sugars in the body and particularly the brain.
Children with Sanfilippo begin showing symptoms of hyperactivity, severe behavioural problems and miss developmental milestones as toddlers. As they get older they show symptoms similar to dementia, and most never achieve a mental age beyond two years. Later they will experience seizures and difficulties in walking and swallowing. It is invariably fatal, with most children dying around the age of 18 years.
Following a licence agreement with Orchard Therapeutics, a new UK-based clinical-stage biotechnology company, the gene therapy developed in Manchester will be trialled in humans. The University of Manchester’s technology transfer company, UMI3, negotiated the terms of the major deal with Orchard Therapeutics.
Dr Brian Bigger, who leads the Stem Cell and Neurotherapies Laboratory at The University of Manchester and developed the technique in partnership with the Trust scientists said: “This license agreement with Orchard will allow us to take the technique we have developed to the next and crucial stage of trials in humans. We are hopeful that this treatment may help to treat the early onset dementia in these patients and saving children’s lives.
“If we can show that it is possible to treat single gene brain diseases, such as Sanfilippo, with stem cell gene therapy, this will pave the way for treating other lysosomal storage and neuro-metabolic disorders”
The treatment works by genetically correcting the patients’ own stem cells and implanting them into bone marrow to release the missing enzyme in a way that reaches the brain, thereby correcting the condition.
The new study will take place at CMFT, supported by the NIHR/Wellcome Trust Manchester Clinical Research Facility.
“There are currently no effective treatments available to children affected by Sanfilippo disease. We hope that this work will help to halt the progression of this devastating condition,” added Dr Simon Jones, Consultant in Paediatric Inherited Metabolic Disease at Saint Mary’s Hospital and the Manchester Centre for Genomic Medicine.
Professor Robert Wynn, Consultant Paediatric Haematologist at Royal Manchester Children’s Hospital and chief investigator for the clinical study explained: “This new clinical study aims to explore whether we can use stem cell gene therapy to produce blood cells that express corrected versions of the missing enzyme.
“We know that in conditions similar to Sanfilippo blood cells from a bone marrow donor can deliver such enzymes effectively. This new gene therapy builds on the decades of experience of CMFT physicians in bone marrow transplantation of children with these other metabolic diseases.”
Earlier attempts to cure the illness with a bone marrow transplant were unsuccessful as not enough enzyme was produced to have an effect, but the Manchester team has developed a way of overproducing the SGSH enzyme specifically in bone marrow white blood cells.
This was achieved by developing a lentiviral vector – a tool commonly used by molecular biologists to deliver genetic material into cells – specifically for use in humans, which will be tested in the trial. The lentiviral vector delivers the SGSH gene to bone marrow cells, which, when implanted into the body are able to traffic to both the bone marrow and the brain and deliver SGSH enzyme throughout the body, thus correcting the disease.
Recently a related illness metachromatic leukodystrophy has been treated by Italian scientists using a similar approach, with extremely promising results in patients.
The Manchester team used a similar lentiviral vector to the Italian team, but improved the design to make it more specific to the white blood cells that traffic into and engraft in the brain after a bone marrow transplant (monocytes/microglia). This improves brain targeting and effectiveness.
Professor Bobby Gaspar, Chief Scientific Officer of Orchard Therapeutics said:“Stem cell gene therapy has shown promising effects in several different diseases and we are hopeful that this technology will change the lives of children with Sanfilippo type A and other monogenic bone marrow disorders in the near future.”
Life Sciences Minister, George Freeman MP, said: “This pioneering trial, led by UK researchers in partnership with a UK company, underlines exactly why we invest £1 billion each year through the National Institute for Health Research.
“This new gene therapy has the potential to change the lives of children with this dreadful condition, and will undoubtedly help to cement the UK’s position as a world-leader in medical research.”
University of Manchester technology Acoustek® won ‘Best University Technology of the Year’ at the UK Energy Innovation Awards 2016 held at the Hilton Manchester Deansgate on Thursday April 28th
Acoustek was first used as a tool for detecting blockages in high pressure natural gas pipelines. Working with Circor the technology is now used routinely in the oil & gas industry to detect and locate blockages at distances of over 10 km. More recently, the technology has been adapted so that it can be applied to locate blockages and other features in gas distribution pipeline networks.
During a two-year project, supported by al four UK gas distribution operators (National Grid, SGN, Northern Gas Networks and Wales & West) the technology has been successfully applied to survey gas distribution pipelines in over 30 trials.
The technology is set to revolutionise the market as the tool designed for the gas distribution market can quickly and accurately locate features at distances of more than 300 m which reduces the number of excavations which must be made to remediate problems and ensures a more rapid resumption of service to customers.
New applications of this versatile technology are being explored through collaboration with a range of partners and adaptations of the technology to new customer needs. For example, inspection companies are able to use the technology to survey heat exchanger tubing and identify corrosion and other damage more quickly than by use of existing methods.
Barry Lennox comments: “The work with the gas distribution operators has proven to be highly successful, with a commercial product expected to be available within the next year or so. Through our engagement with the Energy Innovation Centre and this awards programme, we are hopeful that we will secure the necessary support to see the technology undergo a thorough evaluation around the UK’s gas distribution network.”
For further information about Acoustek, please click here.
The University of Manchester’s ClinTouch project team, led by Professor Shôn Lewis, were runners-up in the Health & Care Award category at the annual AXA PPP Health Tech & You Awards held at BAFTA on 25th April.
Now in its second year, the AXA PPP Health Tech & You Awards is a joint initiative led by AXA PPP healthcare with think tank 2020health and the Design Museum. It aims to guide and grow the conversation about health tech, empowering people everywhere to use technology to lead healthier lives and be more in control of their health and wellbeing.
ClinTouch is a platform to help people with serious mental illness (SMI) to start to manage their own symptoms. It is based around a smartphone app developed by a team of service users, leading clinical and social scientists, software engineers and health professionals at The University of Manchester and funded by the Medical Research Council (MRC) since 2010. ClinTouch’s service user team are central to their design process.
ClinTouch works by tracking people’s symptoms in real time during the day via completion of a personalised item set prompted by semi-random beeps. This takes about a minute to complete. The data are then wirelessly uploaded to a secure central server and a database rapidly built up of symptom patterns, severity and triggers, allowing users to gain increasing control over their illness. An SMS version is available which has been shown to improve users’ experience of care, and enhance collaboration with health professionals.
As well as a standalone app, ClinTouch has been built into an end-to-end clinical management system aimed at averting relapse and rehospitalisation, again funded by the MRC. Following a first episode of SMI, 80% of people have one or more relapses over the next five years, usually leading to acute inpatient admission. Such admissions account for over half of all admissions in NHS mental health services. Treatments for SMI cost the NHS about £2 billion each year.
ClinTouch will alert the care team at the team base if prodromal symptoms of relapse start to emerge, allowing for early community intervention. Data are streamed into e-health records. The system has now been set up and evaluated in mental health Trusts in Manchester and South London. ClinTouch is working directly with several Trusts to facilitate adoption of the technology into the NHS.
ClinTouch has now been beta tested and trialled in about 150 service users with SMI and has been shown to be safe, reliable, valid, and feasible, with high acceptability. Most users like it. The key to this is its design methodology, largely driven by focus groups of people with SMI, which has driven the functionality and usability of the interface. Results of randomised feasibility trials are published in peer-reviewed papers. Specific in-house, personalisable modules, either developed or in development, can be added on to the ClinTouch core: medication management, side effect monitoring, peer-to-peer social networking, simple cognitive behavioural interventions.
Professor Shôn Lewis commented: “The ClinTouch-Affigo team are proud to have been finalists for the health and care award. It shows that our efforts in using innovative technologies to support people with serious mental health problems have been recognised.”
Dr Laura Etchells, Enterprise and Business Development Manager, UMIP, commented: “We are delighted that the project team’s achievements in this space have been recognised by the awards panel as we continue to support the team to explore the commercial potential of the technology.”
Find out more about ClinTouch at www.clintouch.com
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